This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recurrent aphthous stomatitis (RAS) is the most common inflammatory ulcerative disease of the oral cavity in the United States. Genetic and environmental risk factors are thought to play a role in the development of RAS. However, the etiopathogenesis of this disease is still unknown. We will conduct a case-control study to collect epidemiologic data through questionnaires and clinical examinations to determine risk factors for RAS. We will conduct a pilot study of gene expression in RAS and control tissue to gather preliminary data on the role of matrix metalloproteinases (MMPs), their inhibitors (i.e., tissue inhibitors of MMPs and somatostatin), and MMP-related cytokines in the pathogenesis of RAS. Lastly, we will bank data and DNA collected through questionnaires, examinations, blood drawing, and gene expression analyses of biopsy tissue to facilitate future genetic epidemiologic studies of RAS. This is the first study of a series of genetic epidemiologic studies of RAS. The case-control study will provide important information on the role of environmental, socio-economic, and host-related risk factors for RAS. The pilot study will provide new preliminary data on the role of MMPs, their inhibitors, MMP-related cytokines, and other genes in the pathogenesis of RAS. Collectively, the results of this research and the banked data will constitute an important foundation for future epidemiologic studies aimed at understanding the combined role of environmental and genetic risk factors for RAS.